Departmental Papers (BE)

Generalized Langevin dynamics of a nanoparticle using a finite element approach: Thermostating with correlated noise

Uma Balakrishnan et al. — Thu, 13 Oct 2011 10:42:04 PDT

A direct numerical simulation (DNS) procedure is employed to study the thermal motion of a nanoparticle in an incompressible Newtonian stationary fluid medium with the generalized Langevin approach. We consider both the Markovian (white noise) and non-Markovian (Ornstein-Uhlenbeck noise and Mittag-Leffler noise) processes. Initial locations of the particle are at various distances from the bounding wall to delineate wall effects. At thermal equilibrium, the numerical results are validated by comparing the calculated translational and rotational temperatures of the particle with those obtained from the equipartition theorem. The nature of the hydrodynamic interactions is verified by comparing the velocity autocorrelation functions and mean square displacements with analytical results. Numerical predictions of wall interactions with the particle in terms of mean square displacements are compared with analytical results. In the non-Markovian Langevin approach, an appropriate choice of colored noise is required to satisfy the power-law decay in the velocity autocorrelation function at long times. The results obtained by using non-Markovian Mittag-Leffler noise simultaneously satisfy the equipartition theorem and the long-time behavior of the hydrodynamic correlations for a range of memory correlation times. The Ornstein-Uhlenbeck process does not provide the appropriate hydrodynamic correlations. Comparing our DNS results to the solution of an one-dimensional generalized Langevin equation, it is observed that where the thermostat adheres to the equipartition theorem, the characteristic memory time in the noise is consistent with the inherent time scale of the memory kernel. The performance of the thermostat with respect to equilibrium and dynamic properties for various noise schemes is discussed.

Overcoming the Diffraction Limit Using Multiple Light Scattering in a Highly Disordered Medium

Youngwoon Choi et al. — Thu, 14 Jul 2011 09:08:07 PDT

We report that disordered media made of randomly distributed nanoparticles can be used to overcome the diffraction limit of a conventional imaging system. By developing a method to extract the original image information from the multiple scattering induced by the turbid media, we dramatically increase a numerical aperture of the imaging system. As a result, the resolution is enhanced by more than 5 times over the diffraction limit, and the field of view is extended over the physical area of the camera. Our technique lays the foundation to use a turbid medium as a far-field superlens.

Robust Network Topologies for Generating Switch-Like Cellular Responses

Najaf A. Shah et al. — Tue, 28 Jun 2011 08:09:38 PDT

Signaling networks that convert graded stimuli into binary, all-or-none cellular responses are critical in processes ranging from cell-cycle control to lineage commitment. To exhaustively enumerate topologies that exhibit this switch-like behavior, we simulated all possible two- and three-component networks on random parameter sets, and assessed the resulting response profiles for both steepness (ultrasensitivity) and extent of memory (bistability). Simulations were used to study purely enzymatic networks, purely transcriptional networks, and hybrid enzymatic/transcriptional networks, and the topologies in each class were rank ordered by parametric robustness (i.e., the percentage of applied parameter sets exhibiting ultrasensitivity or bistability). Results reveal that the distribution of network robustness is highly skewed, with the most robust topologies clustering into a small number of motifs. Hybrid networks are the most robust in generating ultrasensitivity (up to 28%) and bistability (up to 18%); strikingly, a purely transcriptional framework is the most fragile in generating either ultrasensitive (up to 3%) or bistable (up to 1%) responses. The disparity in robustness among the network classes is due in part to zero-order ultrasensitivity, an enzyme-specific phenomenon, which repeatedly emerges as a particularly robust mechanism for generating nonlinearity and can act as a building block for switch-like responses. We also highlight experimentally studied examples of topologies enabling switching behavior, in both native and synthetic systems, that rank highly in our simulations. This unbiased approach for identifying topologies capable of a given response may be useful in discovering new natural motifs and in designing robust synthetic gene networks.

Nonlinear Inverse Scattering and Three-Dimensional Near-Field Optical Imaging

George Y. Panasyuk et al. — Thu, 23 Jun 2011 09:34:28 PDT

The nonlinear inverse scattering problem for electromagnetic fields with evanescent components is considered. A solution to this problem is obtained in the form of a functional series expansion. The first term in the expansion corresponds to the pseudoinverse solution to the linearized inverse problem. The higher order terms represent nonlinear corrections to this result. Applications to the problem of three-dimensional optical imaging with subwavelength resolution are described and illustrated with numerical simulations.

Comment on "Optical Response of Strongly Coupled Metal Nanoparticles in Dimer Arrays"

Vadim A. Markel — Thu, 23 Jun 2011 09:34:25 PDT

I have recalculated the extinction spectra of aggregates of two silver nanospheres shown in Figs. 2 and 3 of the paper by J. J. Xiao, J. P. Huang, and K. W. Yu [Phys. Rev. B 71, 045404 (2005)]. I have used the approximate method of images according to the formulas published in that reference and an exact numerical technique. I have found that the three sets of data those I have obtained by the method of images, the numerical results, and the results published in the reference in question do not coincide. In this Comment, I discuss the reasons for these discrepancies and the general applicability of the method of images to the quasistatic electromagnetic problem of two interacting nanospheres.

Spectroscopic Studies of Fractal Aggregates of Silver Nanospheres Undergoing Local Restructuring

Sergei V. Karpov et al. — Thu, 23 Jun 2011 09:34:22 PDT

We present an experimental spectroscopic study of large random colloidal aggregates of silver nanoparticles undergoing local restructuring. We argue that such well-known phenomena as strong fluctuation of local electromagnetic fields, appearance of “hot spots” and enhancement of nonlinear optical responses depend on the local structure on the scales of several nanosphere diameters, rather than the large-scale fractal geometry of the sample.

Thermodynamically Equivalent Silicon Models of Voltage-Dependent Ion Channels

Kai M. Hynna et al. — Thu, 02 Jun 2011 08:10:34 PDT

We model ion channels in silicon by exploiting similarities between the thermodynamic principles that govern ion channels and those that govern transistors. Using just eight transistors, we replicate—for the first time in silicon—the sigmoidal voltage dependence of activation (or inactivation) and the bell-shaped voltage-dependence of its time constant. We derive equations describing the dynamics of our silicon analog and explore its flexibility by varying various parameters. In addition, we validate the design by implementing a channel with a single activation variable. The design’s compactness allows tens of thousands of copies to be built on a single chip, facilitating the study of biologically realistic models of neural computation at the network level in silicon.

Propogation of Surface Plasmons in Ordered and Disordered Chains of Metal Nanospheres

Vadim A. Markel et al. — Wed, 11 May 2011 07:24:22 PDT

We report a numerical investigation of surface plasmon (SP) propagation in ordered and disordered linear chains of metal nanospheres. In our simulations, SPs are excited at one end of a chain by a near-field tip. We then find numerically the SP amplitude as a function of propagation distance. Two types of SPs are discovered. The first SP, which we call the ordinary or quasistatic, is mediated by short-range, near-field electromagnetic interaction in the chain. This excitation is strongly affected by Ohmic losses in the metal and by disorder in the chain. These two effects result in spatial decay of the quasistatic SP by means of absorptive and radiative losses, respectively. The second SP is mediated by longer range, far-field interaction of nanospheres. We refer to this SP as the extraordinary or nonquasistatic. The nonquasistatic SP cannot be effectively excited by a near-field probe due to the small integral weight of the associated spectral line. Because of that, at small propagation distances, this SP is dominated by the quasistatic SP. However, the nonquasistatic SP is affected by Ohmic and radiative losses to a much smaller extent than the quasistatic one. Because of that, the nonquasistatic SP becomes dominant sufficiently far from the exciting tip and can propagate with little further losses of energy to remarkable distances. The unique physical properties of the nonquasistatic SP can be utilized in all-optical integrated photonic systems.

Quantum Imaging and Inverse Scattering

John C. Schotland — Tue, 29 Mar 2011 12:07:01 PDT

We consider the inverse scattering problem that arises in two-photon quantum imaging with interferometric measurements. We show that the two-point correlation function of the field contains information about the scattering medium at a spatial frequency of twice the Rayleigh bandwidth. The linearized inverse problem, however, yields reconstructions with a resolution of λ=2, where λ is the wavelength of light.

Can the Imaginary Part of Permeability be Negative?

Vadim A. Markel — Tue, 11 Jan 2011 12:21:07 PST

When new composite optical materials are developed experimentally or studied in numerical simulations, it is essential to have a set of fundamental constraints that the optical constants of such materials must satisfy. In this paper I argue that positivity of the imaginary part of the magnetic permeability may not be one of such constraints, particularly in naturally occurring diamagnetics and in artificial materials that exhibit diamagnetic response to low-frequency or static magnetic fields.

Sequential Effects on the Detectability of a Tone Added to a Multitone Masker

Xiang Cao et al. — Wed, 22 Dec 2010 07:15:53 PST

The detectability of a tone added to a masker is superior when the detection trial is preceded by the masker than the signal-plus-masker. This auditory enhancement can withstand long temporal gaps between the precursor and the trial, suggesting that for yes/no trials sensitivity may depend on the stimulus presented in the prior trial. The results from an experiment examining the detectability of a 1000-Hz tone added to 6-tone maskers confirmed sequential effects on sensitivity. The values of d' were higher when the prior trial was a no-signal (masker alone) trial compared to a signal (signal-plus-masker) trial.

Vector Correlation Technique for Pixel-wise Detection of Collagen Fiber Realignment During Injurious Tensile Loading

Kyle P. Quinn et al. — Tue, 30 Nov 2010 13:29:30 PST

Excessive soft tissue loading can produce adverse structural and physiological changes in the absence of any visible tissue rupture. However, image-based analysis techniques to assess microstructural changes during loading without any visible rupture remain undeveloped. Quantitative polarized light imaging (QPLI) can generate spatial maps of collagen fiber alignment during loading with high temporal resolution and can provide a useful technique to measure microstructural responses. While collagen fibers normally realign in the direction that tissue is loaded, rapid, atypical fiber realignment during loading may be associated with the response of a local collagenous network to fiber failure. A vector correlation technique was developed to detect this atypical fiber realignment using QPLI and mechanical data collected from human facet capsular ligaments (n=16) loaded until visible rupture. Initial detection of anomalous realignment coincided with a measurable decrease in the tissue stiffness in every specimen and occurred at significantly lower strains than those at visible rupture (ρ < 0.004), suggesting this technique may be sensitive to a loss of microstructural integrity. The spatial location of anomalous realignment was significantly associated with regions where visible rupture developed (ρ < 0.001). This analysis technique provides a foundation to identify regional differences in soft tissue injury tolerances and relevant mechanical thresholds.

Nanoscale Optical Tomography using Volume-scanning Near-field Microscopy

Jin Sun et al. — Tue, 30 Nov 2010 13:29:26 PST

The relationship between sample structure and data in volume-scanning backscattering mode near-field optical microscopy is investigated. It is shown that the three-dimensional structure of a dielectric sample is encoded in the phase and amplitude of the scattered field and that an approximate reconstruction of the sample structure may be obtained.

Phaseless Three-Dimensional Optical Nanoimaging

Alexander A. Govyadinov et al. — Tue, 30 Nov 2010 07:58:52 PST

We propose a method for optical nanoimaging in which the structure of a three-dimensional inhomogeneous medium may be recovered from far-field power measurements. Neither phase control of the illuminating field nor phase measurements of the scattered field are necessary. The method is based on the solution to the inverse scattering problem for a system consisting of a weakly-scattering dielectric sample and a strongly-scattering nanoparticle tip. Numerical simulations are used to illustrate the results.

Mechanical Tugging Force Regulates the Size of Cell-Cell Junctions

Zhijun Liu et al. — Tue, 30 Nov 2010 07:58:48 PST

Actomyosin contractility affects cellular organization within tissues in part through the generation of mechanical forces at sites of cell–matrix and cell–cell contact. While increased mechanical loading at cell–matrix adhesions results in focal adhesion growth, whether forces drive changes in the size of cell–cell adhesions remains an open question. To investigate the responsiveness of adherens junctions (AJ) to force, we adapted a system of microfabricated force sensors to quantitatively report cell–cell tugging force and AJ size. We observed that AJ size was modulated by endothelial cell–cell tugging forces: AJs and tugging force grew or decayed with myosin activation or inhibition, respectively. Myosin-dependent regulation of AJs operated in concert with a Rac1, and this coordinated regulation was illustrated by showing that the effects of vascular permeability agents (S1P, thrombin) on junctional stability were reversed by changing the extent to which these agents coupled to the Rac and myosin-dependent pathways. Furthermore, direct application of mechanical tugging force, rather than myosin activity per se, was sufficient to trigger AJ growth. These findings demonstrate that the dynamic coordination of mechanical forces and cell–cell adhesive interactions likely is critical to the maintenance of multicellular integrity and highlight the need for new approaches to study tugging forces.

Injectable Hydrogel Properties Influence Infarct Expansion and Extent of Postinfarction Left Ventricular Remodeling in an Ovine Model

Jamie L. Ifkovits et al. — Tue, 30 Nov 2010 07:58:43 PST

A recent trend has emerged that involves myocardial injection of biomaterials, containing cells or acellular, following myocardial infarction (MI) to influence the remodeling response through both biological and mechanical effects. Despite the number of different materials injected in these approaches, there has been little investigation into the importance of material properties on therapeutic outcomes. This work focuses on the investigation of injectable hyaluronic acid (MeHA) hydrogels that have tunable mechanics and gelation behavior. Specifically, two MeHA formulations that exhibit similar degradation and tissue distribution upon injection but have differential moduli (∼8 versus ∼43 kPa) were injected into a clinically relevant ovine MI model to evaluate the associated salutary effect of intramyocardial hydrogel injection on the remodeling response based on hydrogel mechanics. Treatment with both hydrogels significantly increased the wall thickness in the apex and basilar infarct regions compared with the control infarct. However, only the higher-modulus (MeHA High) treatment group had a statistically smaller infarct area compared with the control infarct group. Moreover, reductions in normalized end-diastolic and end-systolic volumes were observed for the MeHA High group. This group also tended to have better functional outcomes (cardiac output and ejection fraction) than the low-modulus (MeHA Low) and control infarct groups. This study provides fundamental information that can be used in the rational design of therapeutic materials for treatment of MI.

Mining Terabytes of Submillimeter-resolution ECoG Datasets for Neurophysiologic Biomarkers

Jonathan Viventi et al. — Thu, 18 Nov 2010 14:06:39 PST

Recent research in brain-machine interfaces and devices to treat neurological disease indicate that important network activity exists at temporal and spatial scales beyond the resolution of existing implantable devices. We present innovations in both hardware and software that allow sampling and interpretation of data from brain networks from hundreds or thousands of sensors at submillimeter resolution. These innovations consist of novel flexible, active electrode arrays and unsupervised algorithms for detecting and classifying neurophysiologic biomarkers, specifically high frequency oscillations. We propose these innovations as the foundation for a new generation of closed loop diagnostic and therapeutic medical devices, and brain-machine interfaces.

Parallel Hopfield Networks

Robert C. Wilson — Tue, 09 Nov 2010 14:10:24 PST

We introduce a novel type of neural network, termed the parallelHopfield network, that can simultaneously effect the dynamics of many different, independent Hopfield networks in parallel in the same piece of neural hardware. Numerically we find that under certain conditions, each Hopfield subnetwork has a finite memory capacity approaching that of the equivalent isolated attractor network, while a simple signal-to-noise analysis sheds qualitative, and some quantitative, insight into the workings (and failures) of the system.

Ketamine Modulates Theta and Gamma Oscillations

Maciej T. Lazarewicz et al. — Tue, 09 Nov 2010 14:10:19 PST

Ketamine, an N-methyl-D-aspartate (NMDA) receptor glutamatergic antagonist, has been studied as a model of schizophrenia when applied in subanesthetic doses. In EEG studies, ketamine affects sensory gating and alters the oscillatory characteristics of neuronal signals in a complexmanner. We investigated the effects of ketamine on in vivo recordings from the CA3 region of mouse hippocampus referenced to the ipsilateral frontal sinus using a paired-click auditory gating paradigm. One issue of particular interest was elucidating the effect of ketamine on background network activity, poststimulus evoked and induced activity. We find that ketamine attenuates the theta frequency band in both background activity and in poststimulus evoked activity. Ketamine also disrupts a late, poststimulus theta power reduction seen in control recordings. In the gamma frequency range, ketamine enhances both background and evoked power, but decreases relative induced power. These findings support a role for NMDA receptors in mediating the balance between theta and gamma responses to sensory stimuli, with possible implications for dysfunction in schizophrenia.

Radiometric Bimolecular Beacons for Sensitive Detection of RNA in Single Living Cells

Antony K. Chen et al. — Thu, 04 Nov 2010 09:04:31 PDT

Numerous studies have utilized molecular beacons (MBs) to image RNA expression in living cells; however, there is growing evidence that the sensitivity of RNA detection is significantly hampered by their propensity to emit false-positive signals. To overcome these limitations, we have developed a new RNA imaging probe called ratiometric bimolecular beacon (RBMB), which combines functional elements of both conventional MBs and siRNA. Analogous to MBs, RBMBs elicit a fluorescent reporter signal upon hybridization to complementary RNA. In addition, an siRNA-like doublestranded domain is used to facilitate nuclear export. Accordingly, live-cell fluorescent imaging showed that RBMBs are localized predominantly in the cytoplasm, whereas MBs are sequestered into the nucleus. The retention of RBMBs within the cytoplasmic compartment led to >15-fold reduction in false-positive signals and a significantly higher signal-to-background compared with MBs. The RBMBs were also designed to possess an optically distinct reference fluorophore that remains unquenched regardless of probe confirmation. This reference dye not only provided a means to track RBMB localization, but also allowed single cell measurements of RBMB fluorescence to be corrected for variations in probe delivery. Combined, these attributes enabled RBMBs to exhibit an improved sensitivity for RNA detection in living cells.